OBJECTIVES: Qualitative research methods are pivotal to PRO research and the importance of these methods has been highlighted by the FDA draft guidance. The objective of this study was to conduct a review of qualitative methods used in health and social research, to evaluate the methods for application in PRO research, and to develop a methods matrix to enable the selection of the most appropriate methods in a given situation. METHODS: A search was conducted in Medline to identify methods of qualitative data collection and analysis in general, and to identify those methods applied to PRO research since the publication of the FDA draft guidance in February 2006. Qualitative research methods falling were evaluated according to the requirements for valid and reliable PRO research and a methods matrix was prepared. RESULTS: There are a wide variety of methods utilised in health and social research, which are in the broad category of qualitative methods for data collection and analysis. With some approaches, e.g. thematic analysis and grounded theory, there is a need for a tightening of definition in order to reduce some of the ambiguity around methods.  In PRO research qualitative methods are used in concept exploration, selection of PROs, translation of PROs, migration from paper to ePRO, and development/modification of PROs (content validity evidence) among other areas. The results matrix identifies which qualitative methods are the most appropriate for use in specific areas of PRO research. CONCLUSIONS: The ways in which qualitative research methods are applied in PRO research are varied, with some emergence in recent years of alternative theoretical approaches.  The results matrix provides a useful and practical reference to enable selection of a range of qualitative methods for application to solve specific PRO research requirements.